The invention relates to the treatment of separate portions of medical devices such as bioprosthetic devices, with selected, different treatment solutions.
A variety of medical devices such as prostheses can be used to repair or replace damaged or diseased organs, tissues and other structures in humans and animals. Some of these medical devices incorporate tissue or synthetic material as at least a component of the prosthesis. Prostheses generally must be biocompatible due to possible prolonged contact with bodily fluids.
It is often necessary or desirable to treat the natural or synthetic tissue prior to use to improve performance of the prosthetic. Tissue used in prostheses typically is fixed prior to use. Fixation stabilizes the tissue, especially from enzymatic degradation, and reduces antigenicity.
In addition, a prosthesis can be treated with a variety of agents to reduce calcification, i.e., the deposit of calcium salts, particularly calcium phosphate (hydroxyapatite), following implantation in a recipient. Calcification affects the performance and structural integrity of medical devices constructed from these tissues, especially over extended periods of time. For example, calcification is the primary cause of clinical failure of bioprosthetic heart valves. The tissue can also be decellularized in an effort to reduce the effects of calcification and to promote cell growth. Other possible treatments include the application of, for example, antimicrobials, antioxidants and antithrombotics.
Some treatments for medical devices involve the use of potent chemicals, which can result in degradation of delicate portions of the medical device. Also, treatments beneficial to one portion of a medical device may be detrimental to another portion of the bioprosthesis. Furthermore, certain treatments may be appropriate for one portion of a medical device but not other portions due to differences in material or due to the different environments to which the different portions of the medical device may be exposed during use.
The present invention provides for the treatment of different portions of a medical device with different treatment solutions. Therefore, delicate parts of a device can be protected while treating other, less sensitive parts with relatively potent but beneficial treatment solutions. In addition, different portions of a medical device may be in different environments following implantation into a patient. These different portions can be prepared in different ways in preparation for exposure to the different environments. Other advantages of the invention are evident from the description below.
In a first aspect, the invention features an apparatus including:
(a) a first fluid applicator for contacting a first portion of a medical device with a first fluid; and
(b) a second fluid applicator for contacting a second portion of the medical device with a second fluid, the second fluid applicator applying the second fluid in effective isolation from the first portion of the medical device and the first fluid applicator applying the first fluid in effective isolation from the second portion of the medical device.
In some embodiments, the first fluid applicator includes a fluid conduit system including a support system for attaching the fluid conduit system to the medical device such that when attached to the device, fluid flowing through the conduit system contacts a flow region. The support system of the apparatus can include a support that inserts within an opening in the tissue, where the support has a passageway such that fluid flowing through the conduit system flows through the passageway and contacts the first portion of the tissue. The treatment fluid can include a liquid bath, a liquid spray, an aerosol, a gas or a combination thereof.
The apparatus can further include a fastener that holds the tissue against the supports. The fluid applicator can include a container for holding a fluid into which the tissue attached to the conduit system is immersed. In another embodiment, the fluid applicator includes a porous member that direct streams of liquid at the tissue attached to the conduit system.
In another embodiment, the apparatus includes a frame that holds a sheet section of a medical device to facilitate the application of the second fluid in effective isolation from the first portion of the medical device. The first portion can be one side of said sheet section. The second portion can be a side of the sheet opposite the first portion.
In another aspect, the invention features a method of treating a medical device including the steps of:
(a) contacting a first portion of the device with a first fluid such that a second portion of the device is not significantly contacted by the first fluid; and
(b) contacting the second portion of the device with a second fluid substantially different from the first fluid such that the first portion of the device is not significantly contacted by the second fluid.
In some embodiments, the contacting of said first portion involves flowing a first fluid through a fluid conduit system attached to the device such that the fluid flowing through the conduit system contacts the first portion of the device. The fluid conduit system can include a support that inserts within an opening in the device, where the support has a passageway such that fluid flowing through the conduit system flow through the passageway and contacts the first portion of the device.
In the method of treating the device, the contacting of the second portion can be performed by surrounding the tissue with the second fluid, where the second fluid includes a liquid. In an alternative embodiment, the contacting of the second portion is performed by spraying the second portion of the device with the second fluid, where the second fluid can be a liquid. In another alternative embodiment, the contacting step is performed by surrounding the device with the second fluid, where the becond fluid includes a gas.
In another aspect, the invention features an isolated, i.e., ex vivo, vascular tissue including a first region treated with a surface modifying composition and a second region substantially devoid of modification by the surface modifying composition. The surface modifying composition can include, for example, a calcification inhibiting composition such as polyvalent metal cations, an antimicrobial composition, a fixation composition, and/or a decellularization composition such as a composition of digestive enzymes. The first region and/or the second region can be a flow region. Alternatively, the first and second regions can be opposite sides of a sheet material.
In another aspect, the invention features a vascular tissue having an outer decellularized portion and an inner portion substantially devoid of decellularization.
In another aspect, the invention features a vascular tissue having an outer decellularized portion and an inner decellularized portion comprising leaflets, said leaflets substantially maintaining the mechanical properties of the native leaflets.